Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Immunology. 2021 Oct;164(2):305-317. doi: 10.1111/imm.13371. Epub 2021 Jun 6.
Gout is an inflammatory disease triggered by deposition of monosodium urate (MSU) crystals in the joints, resulting in high neutrophil influx and pain. Here, we studied the role of the inhibitory receptor CD300a in the resolution process in a murine model of gout. We found increased CD300a expression on neutrophils emigrated to the joint. When compared to WT mice, CD300a mice had persistent neutrophil influx till 24 hr after MSU injection. This was associated with increased concentration of IL-1β and greater tissue damage in the joints of CD300a mice. There was an increase in the percentage of apoptotic neutrophils in the synovial lavage of WT mice, as compared to CD300a mice. This difference was reflected in the decline of efferocytic events in the synovial cavity of CD300a mice 24 hr after MSU injection. A CD300a agonistic antibody was shown, for the first time, to increase apoptosis of human neutrophils, and this was associated with cleavage of caspase-8. In conclusion, our results reveal an important role of CD300a in the control of leucocyte infiltration, IL-1β production and caspase-8 cleavage in neutrophils, contributing to the resolution of inflammation triggered by MSU injection.
痛风是一种炎症性疾病，由单钠尿酸盐（MSU）晶体在关节中沉积引发，导致大量中性粒细胞浸润和疼痛。在这里，我们在痛风的小鼠模型中研究了抑制性受体 CD300a 在解决过程中的作用。我们发现，迁移到关节的中性粒细胞上表达了更多的 CD300a。与 WT 小鼠相比，CD300a 小鼠在 MSU 注射后 24 小时仍有持续的中性粒细胞浸润。这与 CD300a 小鼠关节中白细胞介素 1β（IL-1β）浓度增加和组织损伤更大有关。与 CD300a 小鼠相比，WT 小鼠滑膜灌洗液中凋亡中性粒细胞的比例增加。这种差异反映在 MSU 注射后 24 小时，CD300a 小鼠滑膜腔中吞噬作用的减少。首次表明，CD300a 激动性抗体增加了人中性粒细胞的凋亡，这与半胱氨酸蛋白酶 8（caspase-8）的裂解有关。总之，我们的研究结果揭示了 CD300a 在控制白细胞浸润、IL-1β 产生和中性粒细胞中 caspase-8 裂解方面的重要作用，有助于控制由 MSU 注射引发的炎症消退。
